1. Field of the Invention
The present invention relates to a method of enantioselective addition to enones and, more particularly, to a method of enantioselective addition of organozinc to enones using a chiral β-amino alcohol.
2. Description of Related Art
Most of isolated natural products have specific stereochemistry. Various stereoconfiguration causes significant difference in bioactivity, and particularly stereoconfiguration is critical for most drugs. For example, thalidomide is a chiral molecule and used for treating sickness and faintness of pregnant women, but its enantiomer causes abnormal fetal development; S,S-isomer of captopril is effective for treating of hypertension and heart disease; and S-isomer of Dopa can be used for treatment of Parkinson's disease, but its R-isomer has toxicity. The U.S. Food and Drug Administration, in 1992, issued that optical isomers of the drug having chiral center(s) should be isolated from each other, studied separately for their bioactivity and taken for clinical testing and only its therapeutically active isomer can be brought to market. Accordingly, many scientists have devoted themselves to the improvement of enantioselectivity to obtain substances having specific stereoconfiguration. The enantioselectivity of products may be enhanced by using chiral reagents, chiral auxiliaries or chiral catalysts, such that products can be synthesized in high optical activity.
Michael addition, also called 1,4-addition or conjugate addition, is one of commonly used methods for forming a C—C bond and widely used in synthesis of natural products and drugs. For example, as shown in Scheme 1, the ketone group on the product from asymmetric 1,4-addition may be modified and transferred into an alcohol or carboxyl group, and bioactive drugs may be obtained through a series of reactions, such as LG121071 (an non-steroidal androgen antagonist), anthracenone (a drug for the treatment of psoriasis), chiral γ-aryl-1H-1,2,4-triazole derivative (an antifungal agent).

Accordingly, it is an important object of the present invention to develop a highly enantioselective conjugate addition.